The major thrust of the studies will be to identify both at cellular level and at the more macroscopic level of the surface mucous coat, the mechanism of protection of the surface cells of the stomach and duodenum against a hostile luminal environment. We will investigate those factors which influence the rate of alkaline secretion in isolated inhibited gastric fundus and in duodenum. The pH gradient across the surface mucous of gastric and duodenal mucosa and the thickness of the mucous gel will be measured with pH microelectrode or a slit lamp and pachymeter in vivo under a variety of experimental circumstances, especially those which affect secretion of mucous and HCO3-. In order to assess more carefully the intracellular events associated with alkaline secretion, and especially to elucidate the intricacies of gastric and duodenal ion transport, electron probe x-ray microanalysis will be used to measure intracellular elements in the various epithelial cells of these tissues. Attempts are under way to grow gastric surface and/or oxyntic cells in refined media with the intent that these will be layered on collagen or fibronectin to be studied in an Ussing chamber. This will allow a more accurate assessment of the detailed physiology of the complex epithelium of the stomach.